Biomedical patch and delivery system

ABSTRACT

A multi-laminar repair matrix for repairing a tissue defect may comprise a top patch and a bottom compliant patch. The bottom compliant patch may be compressed and sized to fit through a tissue defect, and expand to a substantially planar state after being implanted to the tissue defect. The top and/or bottom patch may include adhesives. A tool for implanting a patch to a tissue defect may include a shaft, a plurality of arms pivotally connected to the shaft, and a control. The control may be configured to radially expand the plurality of arms upon actuation of the control.

PRIORITY CLAIM AND INCORPORATION BY REFERENCE

This application claims is a continuation of U.S. patent applicationSer. No. 14/213,216 filed Mar. 14, 2014, and titled “BIOMEDICAL PATCHAND DELIVERY SYSTEM,” which claims priority from U.S. provisional patentapplication No. 61/798,224 filed Mar. 15, 2013. Each of the foregoingapplications is hereby incorporated by reference in its entirety.Further, Patent Cooperation Treaty patent application numberPCT/US2011/040691, filed Jun. 16, 2011 and titled “BIOMEDICAL PATCHESWITH ALIGNED FIBERS,” and claiming priority to U.S. provisional patentapplication No. 61/355712 filed Jun. 17, 2010, are both herebyincorporated by reference herein in their entirety.

BACKGROUND

The embodiments disclosed herein are directed to biomedical patches forrepairing tissue defects, such as dural defects, and delivery systemsapplicable to same.

The human brain and spinal cord are surrounded by a system of threeprotective membranes known as the meninges: the pia mater, the arachnoidmater, and the dura mater. The meninges serve to maintain a layer ofcerebrospinal fluid around the brain and spinal cord, protect the brainand spinal cord from trauma/abrasion, and support extra-corticalvasculature carrying blood to/from the brain. The dura mater is a thickfibrous membrane lining the inner surface of the skull and spinal columnwhich forms a water-tight sac around the central nervous system andserves as the primary barrier between nervous tissue and the underlyingbone. Given the critical role of the dura mater in maintaining a closedlayer of cerebrospinal fluid around the brain and spinal cord, and inprotecting cortical tissue from physical damage/irritation, the health,patency, and structure of the dura mater is essential to proper corticalfunctions.

The dura mater may sustain insults, injuries, or defects by accident,trauma, disease, or through routine surgical procedures. During thecourse of standard neurosurgical procedures the dura mater is commonlyincised, resected, removed, or disrupted and must be repairedintraoperatively. In a large percentage of neurosurgical proceduressurgeons must access anatomical sites within the skull, brain, spinalcord, and spinal column requiring disruption of the native dura mater.In the case of minimally invasive neurosurgical procedures (e.g. burrhole, shunt placement, ablation, etc.), the dura mater may only beminimally incised (defect <1 cm²) to pass small tools into theunderlying nervous tissue. In the case of more invasive neurosurgicalprocedures (e.g. decompressive craniotomy, tumor excision, trauma,etc.), the dura mater may be vastly resected or completely removed(defects >1000-1500 cm²) to allow for cortical decompression or removalof diseased tissues. In all cases, regardless of the size or location ofthe dural defect, the dura mater must be repaired intraopertatively inorder to restore the protective covering of the brain and reestablishthe continuous layer of cerebrospinal fluid around the central nervoussystem. To facilitate this repair surgeons employ a type of surgicalmembrane or patch known as a “dural substitute.”

Dural substitutes may comprise any type of material utilized to repairor replace the dura mater and promote healing and/or regeneration ofnative dura, a process known as “neoduralization”. In all instancesdural substitutes must cover the dural defect, enable a water-tight sealof dural defect, and provide a suitable scaffold for the ingrowth ofnative dural fibroblasts. As a result the majority of dural substitutescomprise a planar material which may be sutured into the native dura orpassively draped over the dural defect to close the dural defect.

SUMMARY

In some embodiments, a repair matrix for repairing a tissue defect maycomprise a compliant patch, wherein the compliant patch is configured tobe compressed and sized to fit through the tissue defect when in a firststate, and the compliant patch is configured to be substantially planarwhen in a second state. The compliant patch may comprise a firstadhesive, the compliant patch may define an outer surface when in thefirst state, and the first adhesive may be located on the outer surface.The compliant patch may comprise electro-spun fibers. The compliantpatch when in the second state may have a shape that follows a perimeterof the tissue defect. The shape of the compliant patch when in thesecond state may be square, rectangular, circular, triangular,elliptical, hexagonal, or quadrilateral. The compliant patch may beconfigured to biodegrade after being implanted to the tissue defect. Insome embodiments, the tissue defect is a dural defect.

In some embodiments, the repair matrix for repairing a tissue defect mayfurther comprise a second patch. The second patch may be complaint. Thesecond patch may comprise a second adhesive. The second patch maycomprise electro-spun nanofibers. The shape of the second patch mayfollow a perimeter of the tissue defect. The shape of the second patchmay be square, rectangular, circular, triangular, elliptical, hexagonal,or quadrilateral. The second patch may be configured to biodegrade afterbeing implanted to the tissue defect.

In some embodiments, a central region of the compliant patch may beadhered to a central region of the second patch via an adhesive. In someembodiments, the compliant patch and the second patch may be separatedby a third layer disposed in between the compliant patch and the secondpatch, wherein the compliant patch is in the second state. The thirdlayer may comprise an adhesive. The third layer may comprise the samematerial as the material of the compliant patch and/or the second patch.The size of the third layer may be smaller than the size of thecompliant patch, and the size of the third layer may be smaller than asize of the second patch, thereby leaving a slot around a peripheralregion of the compliant patch and the second patch.

In some embodiments, a kit for repairing a tissue defect may comprise asterile easily opened packet containing a plurality of patchesconfigured to repair a tissue defect, wherein each patch isprogressively larger and the plurality of patches has same shape,wherein a number and sizes of the patches are such that at least one ofthe plurality of patches is correctly sized to repair a particular knowntype of tissue defect for a range of expected patients. The shape of thepatches may be square, rectangular, circular, triangular, elliptical,hexagonal, or quadrilateral.

In some embodiments, a tool for repairing a tissue defect may comprise ashaft; a plurality of arms pivotally connected to a distal end of theshaft; and a control operably connected to the plurality of arms,wherein the control is configured to radially expand the plurality ofarms upon actuation of the control. The plurality of arms may be biasedradially. The plurality of arms may be configured to receive a compliantpatch in a compressed state, wherein the plurality of arms is configuredto expand a compliant patch loaded onto the plurality of arms from thecompressed state to a substantially planar state upon radial expansionof the plurality of arms. The compliant patch in the compressed statemay be sized to fit through the tissue defect. The complaint patch whenin the substantially planar state may have a square, rectangular,circular, triangular, elliptical, hexagonal, or quadrilateral shape.

In some embodiments, a tool for repairing a tissue defect may comprise aproximal shaft, wherein a distal end of the proximal shaft is configuredto removably connect to a proximal end of a distal shaft that ispivotally connected to a plurality of arms, wherein the proximal shaftcomprises a control configured to operably connect to the plurality ofarms via the distal shaft, wherein the control is configured to radiallyexpand the plurality of arms upon actuation of the control. The tool mayfurther comprise a cartridge for use with the tool, wherein thecartridge comprises the distal shaft and a compliant patch in acompressed state loaded onto the plurality of arms pivotally connectedto the distal shaft, wherein the plurality of arms is configured toexpand the compliant patch from the compressed state to a substantiallyplanar state upon radial expansion of the plurality of arms. Thecompliant patch when in the substantially planar state may have asquare, rectangular, circular, triangular, elliptical, hexagonal, orquadrilateral shape.

In some embodiments, a kit for repairing a tissue defect may comprise apatch delivery system. The patch delivery system may comprise a shaft, aplurality of arms pivotally connected to a distal end of the shaft, anda control operably connected to the plurality of arms, wherein thecontrol is configured to radially expand the plurality of arms uponactuation of the control. The plurality of arms may be biased radially.The tissue defect may be a dural defect. The kit may further comprise apatch having a square, rectangular, circular, triangular, elliptical,hexagonal, or quadrilateral shape. The kit may further comprise acompliant patch in a compressed state loaded onto the plurality of arms,wherein the plurality of arms is configured to expand the compliantpatch from the compressed state to a substantially planar state uponradial expansion of the plurality of arms. The compliant patch in thecompressed state may be sized to fit through the tissue defect. Thecomplaint patch when in the substantially planar state may have asquare, rectangular, circular, triangular, elliptical, hexagonal, orquadrilateral shape.

In some embodiments, a kit for repairing a tissue defect may comprise apatch delivery system. The patch delivery system may comprise a proximalshaft, wherein a distal end of the proximal shaft is configured toremovably connect to a proximal end of a distal shaft that is pivotallyconnected to a plurality of arms, wherein the proximal shaft comprises acontrol configured to operably connect to the plurality of arms via thedistal shaft, wherein the control is configured to radially expand theplurality of arms upon actuation of the control. The kit may furthercomprise saline solution, sutures, gauze, a ruler, or any combinationthereof. The kit may further comprise a patch having a square,rectangular, circular, triangular, elliptical, hexagonal, orquadrilateral shape. The kit may further comprise a cartridge for usewith the patch delivery system. The cartridge may comprise the distalshaft and a compliant patch in a compressed state loaded onto theplurality of arms pivotally connected to the distal shaft, wherein theplurality of arms is configured to expand the compliant patch from thecompressed state to a substantially planar state upon radial expansionof the plurality of arms. The kit may further comprise the distal shaft.The kit may further comprise a compliant patch in a compressed stateloaded onto the plurality of arms pivotally connected to the distalshaft, wherein the plurality of arms is configured to expand thecompliant patch from the compressed state to a substantially planarstate upon radial expansion of the plurality of arms. The compliantpatch when in the substantially planar state may have a square,rectangular, circular, triangular, elliptical, hexagonal, orquadrilateral shape.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a multi-laminar repair matrix applied to a tissuedefect according to one embodiment.

FIG. 2a illustrates a top view of one embodiment of a patch.

FIG. 2b illustrates a perspective view of one embodiment of a patch.

FIG. 3 illustrates a compressed patch according to one embodiment.

FIG. 4 illustrates a method of implanting a patch to a tissue defectaccording to one embodiment.

FIG. 5 illustrates a method of implanting a patch to a tissue defectaccording to one embodiment.

FIG. 6 illustrates a method of implanting a patch to a tissue defectaccording to one embodiment.

FIG. 7 illustrates a method of implanting a patch to a tissue defectaccording to one embodiment.

FIG. 8 illustrates an example of a multi-laminar repair matrix withadhesives according to one embodiment.

FIG. 9 illustrates an example of a multi-laminar repair matrix withadhesives according to one embodiment.

FIG. 10 illustrates two patches adhered together according to oneembodiment.

FIG. 11a illustrates a triangular patch with adhesives according to oneembodiment.

FIG. 11b illustrates a triangular patch with adhesives according to oneembodiment.

FIG. 12a illustrates a square patch with adhesives according to oneembodiment.

FIG. 12b illustrates a square patch with adhesives according to oneembodiment.

FIG. 13a illustrates a rectangular patch with adhesives according to oneembodiment.

FIG. 13b illustrates a rectangular patch with adhesives according to oneembodiment.

FIG. 14a illustrates a patch delivery system according to oneembodiment.

FIG. 14b illustrates a patch delivery system according to oneembodiment.

FIG. 15a illustrates a patch delivery system according to oneembodiment.

FIG. 15b illustrates a patch delivery system according to oneembodiment.

FIG. 16a illustrates a patch delivery system according to oneembodiment.

FIG. 16b illustrates a patch delivery system according to oneembodiment.

FIG. 17 illustrates a patch delivery system with a compressed patchloaded onto the patch delivery system according to one embodiment.

FIG. 18 illustrates a patch delivery system with a planar patch loadedonto the patch delivery system according to one embodiment.

FIG. 19a illustrates a mechanism by which a patch delivery system holdsand releases a patch according to one embodiment.

FIG. 19b illustrates a mechanism by which a patch delivery system holdsand releases a patch according to one embodiment.

FIG. 20a illustrates a mechanism by which a patch delivery system holdsand releases a patch according to one embodiment.

FIG. 20b illustrates a mechanism by which a patch delivery system holdsand releases a patch according to one embodiment.

FIG. 21a illustrates a mechanism by which a patch delivery system holdsand releases a patch according to one embodiment.

FIG. 21b illustrates a mechanism by which a patch delivery system holdsand releases a patch according to one embodiment.

FIG. 22 illustrates a method of implanting a patch to a tissue defectusing a patch delivery system according to one embodiment.

FIG. 23 illustrates a method of implanting a patch to a tissue defectusing a patch delivery system according to one embodiment.

FIG. 24 illustrates a method of implanting a patch to a tissue defectusing a patch delivery system according to one embodiment.

FIG. 25 illustrates a method of implanting a second patch to a tissuedefect using a patch delivery system according to one embodiment.

FIG. 26 illustrates a method of implanting a second patch to a tissuedefect using a patch delivery system according to one embodiment.

FIG. 27 illustrates a method of implanting a second patch to a tissuedefect using a patch delivery system according to one embodiment.

FIG. 28 illustrates a method of implanting a pre-adhered multi-laminarrepair matrix to a tissue defect using a patch delivery system accordingto one embodiment.

FIG. 29 illustrates a method of implanting a pre-adhered multi-laminarrepair matrix to a tissue defect using a patch delivery system accordingto one embodiment.

FIG. 30 illustrates a method of implanting a pre-adhered multi-laminarrepair matrix to a tissue defect using a patch delivery system accordingto one embodiment.

FIG. 31a illustrates a cartridge configured to attach to a patchdelivery system according to one embodiment.

FIG. 31b illustrates the contents of the cartridge of FIG. 31a accordingto one embodiment.

FIG. 32 illustrates a cartridge and patch delivery system detached fromeach other according to one embodiment.

DESCRIPTION

Multiple types of synthetic dural substitutes are available for use inrepairing dural defects created during routine neurosurgical procedures.Yet, despite the present availability of dural substitutes, asubstantial need exists for new dural substitutes that are easier tohandle, increasingly reliable and suturable, increasingly compliant,faster to implant, effectively seal leaks in the dura, promote improvedpatient outcomes, and eliminate injurious side effects andcomplications.

Currently, defects in the dura mater are repaired by implanting a patchto the outer surface of the dura mater. The patch must be sutured orotherwise fixed to the tissue in order to prevent leaks of fluid such ascerebrospinal fluid (CSF) and migration of the patch. In addition, extracare must be taken for defects near the base of the skull where internalpressure is higher and leaks are more likely.

While the embodiments disclosed herein are described with reference tothe dura mater and dural defects, they may be used with any suitablebiological tissue and tissue defects. For example, the embodimentsdisclosed herein may be used in neosurgery, reconstructive surgery,plastic surgery, general surgery, minimally invasive surgery, orthopedicsurgery, gastroenterology, wound care, and the like. Further, as usedherein, the term “patch” may include a dural substitute, graft, mesh,membrane, scaffold, matrix, substrate, or replacement for any suitablebiological tissue.

Because fluid inside the dura mater exerts an outward force, leaks wouldbe more effectively prevented by implanting a patch to the inner surfaceof the dura mater. The need to suture and/or the small size of a duraldefect, however, currently make it impractical to implant a patch to theinner surface.

Accordingly, the embodiments disclosed herein provide systems andmethods for repairing a defect in a tissue, such as a dural defect, byimplanting a patch to the inner surface of the tissue. In addition, asecond patch may be implanted to the outer surface of the tissue defect.Adhesives may be included on the patch according to some embodiments ofthe invention in order to secure the patch to the tissue. The patch withadhesives may be used to repair a tissue defect from the outer surface,inner surface, or both. In addition, the shape of the patch and/oradhesives may be customized to repair the particular tissue defect beingrepaired. The embodiments disclosed herein further provide a system fordelivering a patch to a tissue defect and encouraging effective cellularingrowth and repair of a tissue defect.

FIG. 1 illustrates a side cross-sectional view of a multi-laminar repairmatrix 100 according to some embodiments of the invention. FIG. 1illustrates a top patch 140 and a bottom patch 120 implanted over atissue defect 110, such as a dural defect. Referring to FIG. 1, the toppatch 140 is applied to the outer surface 150 of the tissue defect 110,thereby patching the tissue defect 110. Still referring to FIG. 1, thebottom patch 120 is applied to the inner surface 130 of the tissuedefect 130, thereby plugging the tissue defect 110. Some embodiments maycomprise one or more layers of patches, both beneath and above thetissue defect 110. Referring to FIG. 1, patches 120, 140 may be largerthan the tissue defect 110 such that the peripheral regions 840 of thepatches 120, 140 contact the tissue surrounding the defect 110. Such aconfiguration may promote optimal closure of the defect 110 from allsides and approximate the surrounding tissue.

The materials, mechanical properties, and/or biological properties ofthe top patch 140 may be different from the bottom patch 120. In otherembodiments, the materials, mechanical properties, and/or biologicalproperties of the top patch 140 may the same as the bottom patch 120.The material of the patches 120, 140 may be polymeric or biologicoptimized to promote cellular adhesion and/or tissue ingrowth.

In addition, the size, shape and/or geometry of the top patch 140 may bedifferent from the bottom patch 120. In other embodiments, the size,shape and/or geometry of the top patch 140 may be the same as the bottompatch 120. In some embodiments, the bottom patch 120 may be smaller thanthe top patch 120. The small size of the bottom patch 120 may allow thebottom patch 120 to be inserted through the tissue defect 110. With thelarger size of the top patch 140, a larger portion of the patch 140 maycontact the tissue, thus promoting cellular ingrowth and sealing of thetissue defect 110. In addition, in order to prevent foreign bodyresponse, inflammatory response, and/or allergic response, the size ofthe top patch 140 may be limited. For example, the patch 120, 140 mayextend over the tissue defect 110 such that there is sufficient contactbetween the tissue and the patch 120, 140 to promote cellular ingrowthand sealing of the tissue defect 110, without causing a foreign bodyresponse, an inflammatory response, and/or an allergic response. Thus,in some embodiments, the size of the top patch 140 may be optimized topromote cellular ingrowth and sealing while preventing foreign bodyresponse, inflammatory response, and/or allergic response. In someembodiments, the general shape of the top 140 and bottom 120 patches maybe the same, although the patches 120, 140 may be different in size.

Further, the thickness of the top patch 140 may be different from thebottom patch 120. In other embodiments, the thickness of the top patch140 may be the same as the bottom patch 120. In some embodiments, thethickness of the bottom patch 120 may be thinner than the top patch 140.The thinness of the bottom patch 120 may allow for greater flexibilityand compliancy, so that the bottom patch 120 may be compressed andinserted through a tissue defect 110. The thickness of the top patch 140may be thicker than the bottom patch 120, so that strength may be addedto the multi-laminar repair matrix 100. In some embodiments, thethickness of the patch 120, 140 is between about 0.1 mm and 4 mm. Insome embodiments, the side of the patch 120, 140 in contact with thetissue and directly proximate to the tissue defect 110 may promotecellular adhesion and/or tissue ingrowth. Thus, cellular ingrowth mayoccur in the tissue defect 110. In addition, the other side of the patch120, 140 facing away from the tissue may prevent cellular adhesionand/or tissue ingrowth. Otherwise, cellular adhesion and/or tissueingrowth on the side of the patch 120, 140 facing away from the tissuedefect 110 may disadvantageously cause the patch 120, 140 to grow intothe tissue.

FIG. 2a illustrates a top view of a patch 120 in a planar state and FIG.2b illustrates a perspective view of a patch 120 in a planar state.While FIGS. 2a-2b illustrate a circular patch 120, the patch 120 can beany shape, as further described herein. FIG. 3 illustrates a patch 120in a compressed state. As illustrated in FIG. 3, in some embodiments,the patch 120 in a compressed state can resemble the canopy of a closedumbrella. FIGS. 4-6 illustrate a method of implanting a bottom patch 120to the inner surface 130 of a tissue defect 110. In some embodiments, amethod of implanting a bottom patch 120 to the inner surface 130 of atissue defect 110 includes compressing the patch 120 from a planar stateto a compressed state. In some embodiments, a patch 120 is pre-packagedin a compressed state. Referring to FIG. 4, the compressed patch 120 isthen inserted through a tissue defect 110. In some embodiments, thebottom patch 120 may be implanted without drastic compression of thepatch 120. For example, the tissue defect 110 may be sized such that abottom patch 120 can be inserted through the tissue defect 110 withoutdrastic compression of the patch 120. Referring to FIGS. 5-6, once thepatch 120 is below the tissue defect 110, it is expanded to asubstantially planar state. The patch 122 may be positioned as necessaryso that it completely covers the tissue defect 110. Further, the patch120 may be positioned to be flush against the tissue surrounding thedefect 110, promoting intimate contact and repair of the tissue defect110. Referring to FIG. 7, in some embodiments, a top patch 140 may alsobe implanted to the outer surface of the tissue defect 110. Further, insome embodiments, adhesives may be included on the top and/or bottompatch 120, 140 to secure the patches 120, 140 to the tissue defect 110or to secure the patches 120, 140 to each other. The bottom patch 120and/or top patch 140 may be implanted using a patch delivery system,which is further described herein.

In some embodiments, the bottom patch 122 is compliant so that it may becompressed and sized to fit through a tissue defect 110. In addition, abottom patch 120 that is compliant can conform to the curvature of thetissue surrounding the defect 110, thereby forming a complete seal andminimizing the possibility of leaks. In some embodiments, a patch 120,140 may become more complaint and flexible when hydrated. A compliantpatch may comprise a dural substitute formed by electro-spinningmethods, as described in PCT/US2011/040691, the entirety of which ishereby incorporated herein by reference. Accordingly, in someembodiments, the patches 120, 140 described herein may compriseelectro-spun fibers. The fibers may comprise nanofibers, microfibers, ora combination of both. In some embodiments, the thickness of the patch120, 140 is between about 0.1 mm and 4 mm.

Adhesives or adhesive properties may be included on or in the top patch140 and/or bottom patch 120 for adhering the patch to a tissue oranother patch and aid in patching and/or plugging a tissue defect 110.In some embodiments, the adhesives can be separate components from thepatch 120, 140. In other embodiments, the adhesive property can beengineered into the material comprising the patch 120, 140. In someembodiments, the adhesive property can be integrally formed with thepatch 120, 140. In some embodiments, the patch 120, 140 may comprisenano-fibers with electro static properties, thus exhibiting adhesiveproperties. In addition, the patch 120, 140 may exhibit adhesiveproperties in any number of additional ways. For example, the patch 120,140 may be specially treated such that the patch exhibits adhesiveproperties. As used herein, it will be appreciated that references toadhesives may include any combination of the above.

The adhesives may be included on a patch 120, 140 in any number ofdifferent configurations or manners. For example, a patch 120, 140 mayinclude any shaped adhesive, continuous adhesives, or discreteadhesives. In addition, adhesives may be included on the bottom patch120 only, the top patch 140 only, and/or both the top 140 and bottompatch 120. The adhesive may be deposited onto a patch 120, 140 (orintegrated onto the patch 120, 140, engineering into the patch 120, 140,etc.) in any number of ways, such as mask deposition, spray adhesive,stamping, coating, etc. In some embodiments, neither the top patch 140nor bottom patch 120 includes adhesives.

In some embodiments, one side of a patch 120, 140 is wholly coated withadhesive (or adhesive is integrated onto the patch 120, 140, engineeringinto the patch, etc). In some embodiments, coating a patch 120, 140 withadhesive does not change the porosity of the patch 120, 140. Forexample, a patch 120, 140 may comprise a series of interconnectedfibers, with pores or spaces between the connection points of thefibers. The patch 120, 140 may be coated with adhesive such that theadhesive coats the fibers, while leaving undisturbed the pores or spacesin the patch 120, 140. Accordingly, the adhesive does not detract fromthe rate and quality of cell ingrowth in the pores or spaces. Inaddition, in some embodiments, the adhesive does not detract from otherproperties of the patch 120, 140, such as mechanical properties,biocompatibility, handing, ease of use, implantation, and intraoperativedelivery.

The adhesive can comprise more than 90%, 80%, 70%, 60%, 50%, 40%, 30%,20%, 10%, or less of the patch area. According to some embodiments, theamount of adhesive covering a patch 120, 140 does not affect thecompliancy of the patch 120, 140. In addition, in some embodiments, theamount of adhesive does not affect the flexibility, handling, and feelof the patch 120, 140 in some embodiments. In some embodiments, thecompliancy of the patch 120, 140 is insignificantly reduced by theamount of adhesive.

FIGS. 8-9 illustrate side views of a first patch 810 and a second patch820 with exemplary configurations of adhesives830. It will beappreciated that “first patch” and “second patch” are used forconvenience to refer to a multi-laminar repair matrix 100 comprising atop patch 140 applied to the outer surface of a tissue defect 110 and abottom patch 120 applied to the inner surface of the tissue defect 110,and that “first” or “second” does not necessarily refer to the top patch140 or bottom patch 120. Thus, “first” may refer to a top patch 140 and“second” may refer to a bottom patch 120, or “first” may refer to abottom patch 120 and “second” may refer to a top patch 140.

Referring to FIG. 8, two patches 810, 820 may be wholly covered withadhesive 830. Thus, when implanted, the peripheral regions840 of thepatches 810, 820 may adhere to the tissue surrounding the defect 110.Further, the adhesive 830 at the central region 850 of the first patch810 may adhere through the tissue defect 110 to the adhesive 830 at thecentral region 850 of the second patch 820.

Referring to FIG. 9, the first patch 810 is covered by adhesive 830 andthe second patch 820 does not include any adhesives 830 according tosome embodiments of the invention. The patches 810, 820 may be implantedso that the peripheral region840 of the first patch 810 adheres totissue and adhesive 830 at the central region 850 of the first patch 810adheres through a tissue defect 110 to the central region 850 of thesecond patch 820.

The adhesive 830 can promote faster healing time, improve quality repairof the tissue defect 110, and improve patient outcomes. Adhesive 830between the tissue and patch 120, 140 can enhance the apposition andadhesion of the patch 120, 140 to the tissue, increase the strength ofthe seal, facilitate a water-tight seal, and encourage tissue ingrowthinto the patch 120, 140 by promoting intimate contact with the tissueand cell sources/populations. Further, reinforcing tissue leads to lowerrisk of leaks. Similarly, adhesive 830 securing a top patch 140 and abottom patch 120 to each other over a tissue defect 110 can promotesecure closure of the tissue defect 110, a complete seal of theperipheral tissue, and cellular infiltration leading to regeneration ofnative tissue. Additionally, adhesives 830 securing a patch 120, 140 toa tissue, or adhesives 830 securing a patch 120, 140 to another patch120, 140 through a tissue defect 110, may prevent migration of the patch120, 140 and dehiscence and improve rates of defect sealing and woundhealing.

Although FIGS. 8-9 illustrate adhesives on a multi-laminar system 100,adhesives may be used with a single-laminar system as well. In addition,in some embodiments, a multi-laminar system 100 does not include anyadhesives.

Referring to FIG. 10, in some embodiments, two patches 120, 140 can beadhered to each other pre-operatively. For example, a central region 850of the two patches 120, 140 can be adhered to each other, and theperipheral regions 840 of the patches 120, 140 may be free ofadhesives830. In some embodiments, the central region 850 of bothpatches 120, 140 may include adhesives 830 to adhere to each other, asillustrated in FIG. 10. In other embodiments, the central region 850 ofonly one patch 120, 140 may include adhesive, to adhere to the centralregion 850 of the other patch 120, 140. In some embodiments, the patches120, 140 may have a radius of about 5 cm and the adhesives 830 may havea radius of about 3 cm. Thus, in some embodiments, a multi-laminarrepair matrix may comprise patches 120, 140 that are pre-adheredpre-operatively. The pre-adhered multi-laminar repair matrix may beimplanted to a tissue defect 110 such that the area of adhesion 1010between the two patches 120, 140 is aligned with the tissue defect 110,and the tissue surrounding the tissue defect 110 is disposed in betweenthe un-adhered peripheral regions 840 of the patches 120, 140. Theseparation distance between the und-adhered peripheral regions 840 ofthe two patches 120, 140, illustrated by the arrow 860 in FIG. 10, maybe designed to approximate the thickness of a tissue surrounding atissue defect 110. The patches 120, 140 may be connected to each otherwith the central regions 850 connected and the peripheral regions 840unconnected according to any suitable mechanism known in the art.

In some embodiments, two patches 120, 140 may be separated by a smallerintermediate patch in between the two patches 120, 140. Thus, referringto FIG. 10b , in some embodiments, instead of adhesive 830, anintermediate patch can be located in its place. Thus, in someembodiments, a multi-laminar repair matrix 100 may include three layersof patches 120, 140. In some embodiments, the materials of the threelayers of patches 120, 140 may be the same. In other embodiments, thematerials of the three layers of patches 120, 140 may vary.

In some embodiments, the shape of the patches 120, 140 may vary from thestandard square geometry shape wherein the patch 120, 140 is shaped as asquare with equal length and width and constant thickness. In amulti-laminar repair matrix 100, the top patch 140 and/or bottom patch120 may have a shape that varies from the standard square geometryshape. In a single-laminar repair matrix comprising only one patch 120,140, which may be implanted to the inner surface or outer surface of atissue defect 110, that single patch 120, 140 may also have a shape thatvaries from the standard square geometry shape. In addition, inembodiments where adhesives 220 are included on the patch 120, 140, theshape of the adhesive 220 may similarly vary. Many shapes are possiblefor the patch 120, 140 and/or adhesives 220. In some embodiments, thesize of the patch 120, 140 and/or adhesives 220 may vary depending onits application and the size of the tissue defect 110.

For example, in some embodiments, the shape of the patches 140, 120match the shape of a tissue defect 110. For example, the patches 120,140 can have a shape that follows the perimeter of the tissue defect110. For example, for procedures leaving a triangular shaped defect 110in a tissue, the patches 120, 140may be triangular, as illustrated inFIGS. 11a -b. Thus, the patch 120, 140 may define a triangle. In someembodiments, the length of the base of the triangular shaped patch 120,140 may be between about 0.5 cm and 10 cm, the height of the triangularshaped patch 120, 140 may be between about 1 cm and 20 cm, and the angleat the vertices of the triangular shaped patch 120, 140 may be betweenabout 5° to about 85°. In some embodiments, a triangular shaped patch120, 140 may have a base of about 4 cm and a height of about 8 cm. Sucha configuration may be optimized for surgical repair of defects in theposterior fossa, such as surgical repair of Chiari malformations. Inthese embodiments, the material of the patch 120, 140 may be designedwith added thickness and mechanical strength to withstand increasedbiological pressure applied to the patch 120, 140 following surgicalimplantation.

Additionally, as illustrated in FIG. 11a , a hollow triangular shapedadhesive 830 may be included on the peripheral region 840 of the top 140and/or bottom patch 120. Thus, the adhesive 830 may define a hollowtriangle. Referring to FIG. 11b , the central region 850 of the top 140and/or bottom patch 120 may also include a triangular shaped adhesive830. Thus, the adhesive 830 may define a triangle.

In some embodiments, the patch 120, 140 may be circular and have adiameter of less than 1 cm to more than 10 cm. In some embodiments, theradius of a circular patch 120, 140 can be between about 0.5 cm and 10cm. For example, a circular patch 120, 140 may have a radius of about 5cm. Such a configuration may be optimized for repairing tissue defectsin the cranium or calvarium, such as surgical excision of tumors orneoplasms. In these embodiments, the patch 120, 140 may be designed withreduced mechanical strength yet increased resistance to externallydelivered radiation, increased sealing capabilities, and optimizedcellular or tissue ingrowth following surgical implantation. In otherembodiments, a circular patch 120, 140 may have a radius of about 0.5cm. Such a configuration may be optimized for repair of tissue defectsin and around the spine and spinal cord, which may occur during commonspinal fusion or instrumentation procedures. In these embodiments, thematerial of the patch 120, 140 may be designed with increased mechanicalstrength and increased sealing capabilities.

In some embodiments, a circular patch 120, 140 with a radius of about 5cm may also include a circular shaped adhesive 830 in the center of thepatch 120, 140. The circular shape adhesive 830 may be 3 cm in someembodiments.

In some embodiments, the shape of the patch 120, 140 may be elliptical.For example, the long axis of the patch 120, 140 may be between about 1cm and 20 cm, and the short axis may be between about 0.5 cm and 10 cm.In some embodiments, an elliptical patch may have a short axis of about3 cm and a long axis of about 10 cm. Such a configuration may beoptimized for surgical repair of defects in the posterial fossa, such assurgical repair of Chiari malformations. In these embodiments, the patch120, 140 may be designed with added thickness and mechanical strength towithstand increased biological pressure applied to the patch 120, 140following surgical implantation.

In some embodiments, the shape of the patch 120, 140 may be hexagonal.For example, a hexagonally shape patch may have a length and widthbetween about 1 cm and 20 cm.

In some embodiments, the shape of the patch 120, 140 may bequadrilateral. For example, a quadrilateral patch 120, 140 may have abase between about 1 cm and 10 cm, and the height of the quadrilateralpatch 120, 140 may be between about 0.5 cm and 10 cm.

In some embodiments, the patch 120, 140 may have a constant thickness.For example, the thickness of the patch 120, 140 may be between about0.1 mm and 4 mm. In other embodiments, the patch 120, 140 may have avariable thickness. For example, the variable thickness may be designedaccording to the local mechanical and biological properties of thetissue defect 110.

In addition, adhesive 830 placed in a central region 850 of a patch 120,140 may define a shape resembling that of the tissue defect 110.Further, adhesive 830 placed in a peripheral region 840 of a patch 120,140 may define a hollow shape resembling that of the tissue defect 110.Thus, the patches 120, 140 and/or adhesives 830 may be square,rectangular, oval, etc. FIGS. 12a-b and 13a-b illustrate some exemplaryshapes of patches 120, 140 with adhesive 830.

FIGS. 12a-b illustrate patches 120, 140 customized for repairing tissuedefects 110 having a square shape. Specifically, the shape of thepatches 120, 140 may be square. In addition, the patch 120, 140 mayinclude adhesive 830 in the shape of a hollow square, as illustrated inFIG. 12 a. In another embodiment, the patch 120, 140 may includeadhesive 830 in the shape of a square located at the center 850 of thepatch 120, 140, as illustrated in FIG. 12b . FIGS. 13a-b illustratepatches customized for repairing tissue defects 110 having a rectangularshape.

In some embodiments, the shapes and sizes of the top 140 and bottom 120patches may be different. In addition, the shapes and sizes of theadhesives 220 on the top 140 and bottom 120 patches may be different.For example, the bottom patch 120 may be a relatively large circularshaped patch 120 for plugging a tissue defect 110, and the top patch 120may be a relatively smaller circular shaped patch 140 for suturing in tothe tissue surrounding the tissue defect 110. Additionally, the patches120, 140 may be customized in any number of different ways besides theshape and size. For example, the composition, mechanical properties,design, material, and fixation method can be specifically tailored for acertain tissue defect.

Accordingly, the multi-laminar repair matrix 100 and/or single laminarrepair matrix and customized designs can provide superior outcomespost-operatively due to customization of the repair matrix to the tissuedefect 110. In some embodiments, the repair matrix is pre-packaged andpre-customized by type of tissue defect 110. Thus, in some embodimentsthe repair matrix does not require significant shaping or customizationfor use in repairing a tissue defect 110. The pre-customized packagescan improve the intraoperative efficiency of surgeons. Instead ofhand-cutting patches in the operating room to fit a tissue defect 110,the surgeon can simply select the proper customized package for theappropriate tissue defect 110. In addition, the pre-customized repairmatrix may have the benefits of more rapid deployment and implantationtime, superior fit to the tissue defect 110, optimized mechanicalproperties pertaining to the tissue defect 110, and optimized biologicalproperties pertaining to the tissue defect 110.

The adhesive 830 can promote faster healing time, improved qualityrepair of the tissue defect 110, and improved patient outcomes. Adhesive830 between the tissue and patch 120, 140 can enhance the apposition andadhesion of the patch to the tissue, increase the strength of the seal,facilitate a water-tight seal, and encourage tissue ingrowth into thepatch by promoting intimate contact with the tissue and cellsources/populations. Similarly, adhesive 830 securing a top patch 140and a bottom patch 120 to each other over a tissue defect 110 canpromote secure closure of the tissue defect 110, a complete seal of theperipheral tissue, and cellular infiltration leading to regeneration ofnative tissue. Additionally, adhesives 830 securing a patch 120, 140 toa tissue or adhesives 830 securing a patch 120, 140 to another patch120, 140 through a tissue defect 110 can prevent migration of the patchand dehiscence.

The adhesives 830 can be made from any suitable materials, such asbiologically derived adhesives (fibrin, fibronectin, collagen, etc.),synthetic adhesives (PEG/PEG hydrogels, acrylic solutions, cyanoacrylatesolutions, 2-octyl cyanoacylate, epoxy solutions, etc.)electrostatic/surface forces (electric charge, charge buildup, etc.),mechanical adhesion (fiber structure, entanglement, etc.). Further, theadhesives 830 can be formed onto the patch 120, 140 in any number ofways, such as chemical crosslinking, prolonged thermal processing,moderate mechanical entanglement, application of moderate adhesives,high-pressure physical lamination, or any other suitable method. In someembodiments, the material of the patch 120, 140 and/or the material ofthe adhesives 830 may include fibrin and/or cyanoacrylate. Fibrin andcyanoacrylate are generally known to have good adhesion properties forbiological tissues. In addition, fibrin may be a natural structuralelement of native tissue, thus allowing cells to more rapidly bind ontothe patch 120, 140 and/or adhesive 830 and migrate into the patch 120,140.

In some embodiments, adhesives 830 are included on a patch 120, 140 thatis compliant and conforms to the curvature of the tissue surrounding thedefect 110. A compliant patch 120, 140 can increase the area of contactbetween the patch 120, 140 and the tissue. Thus, adhesives 830 may beplaced anywhere throughout the patch 120, 140 and still adhere to tissuesurrounding a defect 110 and/or to another patch 120, 140 through thetissue defect 110. In some embodiments, the bottom patch 120 and/or toppatch 140 is compliant. Compliant patches 120, 140 can also increasehandling, save time in the operating room, improve ease of use, andimprove suturability.

The top patch 140 may be secured by adhesives only, sutures only, bothadhesives and sutures, or any fixation technique known in the art. Thus,the top patch 140 may be secured by suturing, stapling, tacking,tucking, folding, pinning, crimping, sealing, tissue welding, gluing,fusing, adhesives, or any combination thereof. In some embodiments, thetop patch 140 is implanted according to “onlay” techniques known in theart. The bottom patch 120 may be secured to the tissue defect 110 byadhesives 830 according to some embodiments of the invention. In someembodiments, the bottom patch 120 does not include adhesive 220, but thetop patch 140 includes adhesive 830 for adhering to the bottom patch120. Some embodiments provide for a multi-laminar repair matrix 100without any adhesives 830, neither on the top patch 140 nor the bottompatch 120. External force exerted by fluid, such as cerebrospinal fluidin the dura mater, can help keep the bottom patch 120 in place and pluga tissue defect 110. Even without any adhesives 830, the multi-laminarrepair matrix 100 achieves a high quality seal due to the additionallayer of patch 120, 140 beneath the tissue defect 110.

In some embodiments, the adhesive elements 830 are used in asingle-laminar patch system. For example, adhesives 830 may be includedon the peripheral region 840 of a bottom patch 120 for adhering to theinner surface 130 of the peripheral tissue surrounding a defect 110. Insome embodiments, a top patch 140 is not implanted. In otherembodiments, a top patch 140 is implanted to the outer surface of atissue defect 110 but a bottom patch 120 is not implanted. The top patch140 may include adhesive elements 830 for adhering to the outer surfaceof the tissue defect 110. The adhesives 830 and patch 120, 140 in asingle laminar patch system may follow any number of different shapes,sizes, patterns, and configurations, as explained above with respect tothe multi-laminar repair matrix 100.

Some embodiments include a single-laminar patch, such as a bottom patch120, without any adhesives 830. External force exerted by fluid, such ascerebrospinal fluid in the dura mater, can help keep the bottom patch120 in place and plug a tissue defect 110.

In some embodiments, the adhesive 830 may biodegrade and/or lose itsadhesive properties after a certain amount of time. Some embodimentsinclude a resorbable patch 120, 140 that biodegrade followingimplantation of the patch 120, 140 to a tissue defect 110. In someembodiments, the timing of resorbtion of the patch 120, 140 can becontrolled. The adhesive 830 may last until the patch 120, 140biodegrades or the adhesive 830 may last longer than the time it takesfor the patch 120, 140 to biodegrade. For adhesives 830 adhering a patch120, 140 to the peripheral tissue surrounding a tissue defect 110, thebiodegrading time may be the same as the patch 120, 140 biodegradingtime. For adhesives 830 adhering two patches 120, 140 together through atissue defect 110, the biodegrading time may be longer than the patch120, 140 biodegrading time. The adhesive 830 may also be designed tolast until cells grow over the patch 120, 140, cells grow into the patch120, 140, or the patch 120, 140 is integrated into the surroundingtissue. In some embodiments, the adhesive 830 biodegrading time is thesame as, or longer than, the time it takes for substantial cell ingrowthinto the patch 120, 140. A patch 120, 140 may include adhesives 830 withdifferent biodegrading times on different regions of the patch 120, 140.In some embodiments, the biodegrade time of adhesive 830 on one patch(e.g. a bottom patch 120) is different than the biodegrading time ofadhesive 830 on the other patch (e.g. a top patch 140). The biodegradetime of the adhesive 220 can range anywhere from less than a week toindefinitely (e.g. the adhesive 220 may not ever lose its adhesivequalities).

The adhesives 830 may further be utilized to adhere two patches 120, 140together and thereby alter the strength of a patch 120, 140. Forexample, two patches 120, 140 adhered to each other via multiplerestricting adhesion points provide rigidity and structure support.Further, different parts of a patch may be designed to exhibit differentstrengths. For example, two patches 120, 140 may be adhered to eachother at the center of the patches 120, 140. Accordingly, the overallflexibility and compliance of the patches 120, 140 may be changed.

The bottom 120 and/or top patch 140 may be deployed to a treatment siteusing the delivery system 1400 illustrated in FIG. 14a . FIG. 14aillustrates a patch delivery system (“PDS”) 1400 with a shaft 1430,distal arms 1410, and a control 1420. The PDS 1400 may be made fromplastic and/or surgical grade metal such as titanium alloy or nitinol.In some embodiments of the invention, the distal end of the shaft 1430branches off into distal arms 1410 that are pivotally connected to theshaft 1430 at one or more connection points 1450. The distal arms 1410provide a structural frame and support for holding a patch 120, 140 in acompressed state. The PDS 1400 may further include a control 1420operably connected to the distal arms 1410. In some embodiments, thecontrol 1420 is located toward the proximal end of the shaft 1430.Further, the length of the shaft 1430 may be variable. The distal arms1410 may be made of nitinol, surgical grade stainless steel, or anyother suitable material known in the art. In some embodiments, thedistal arms 1410 may be thin so that they are flexible.

In some embodiments, the PDS 1400 includes a handle 1440 at the proximalend of the shaft 1430 for interoperative handling of the PDS 1400. Thecontrol 1420 may be placed at or near the handle 1440. The proximal endof the shaft 1430 may also include one or more Luer ports, check valveand similar components for infusion or aspiration of fluid and medicine.For example, the ports may allow the hydration of a patch prior todelivery. Such components are well known in the art.

The control 1420 may operate the distal arms 1410 by delivering amechanical force or an electrical signal to the distal arms 1410. Insome embodiments, the PDS 1400 is battery powered and/or wireless. Themechanical force may include a linear force, a torque, a stress, astrain, or other mechanical force. The mechanical force may be appliedby a user's hand or robotic control and may be applied to the control1420 on the PDS 1200. The electrical signal may include an electricalcurrent, an electrical change in voltage, or other electrical signal. Insome embodiments, the electrical signal controls the distal arms 1410through a motor or other mechanism.

Referring to FIG. 14a , the distal arms 1410 may be axially aligned withthe axis of the shaft 1430 when the distal arms 1410 are in a firstposition. Referring to FIG. 14b , when the distal arms 1410 are in asecond position, the distal arms 1410 may expand radially from the shaft1430. Multiple other methods of arm deployment are possible. The distalarms 1410 may be extended from an axial position to a radial position byactuating the control 1420. The control 1420 may be a trigger, switch,button, knob or the like. The control 1420 may be configured to expandthe distal arms 1410 radially in any number of ways. The control 1420further includes a mechanism for returning the distal arms 1410 to anaxial position, described herein as “releasing” the control 1420. Thecontrol 1420 may be released by moving a switch, knob, trigger,actuator, controller, etc. to another position. In another embodiment,the control 1420 includes two buttons, one for radially expanding thedistal arms 1410 and one for compressing the distal arms 1410 to anaxial position. The control 1420 may be released and actuated via any ofthe above and via any mechanism known in the art.

Referring to FIG. 15a , in some embodiments, the distal arms 1410 arecontained within a distal tube 1510 attached to the distal end of theshaft 1430. The distal arms 1410 may be contained in an axial positionwhen inside the distal tube 1510 and biased radially so that when thedistal arms 1410 are positioned outside the distal tube 1510, the distalarms 1410 expand radially, as illustrated in FIG. 15b . The distal arms1410 may be positioned outside the distal tube 1510 by applying an axialdistal force, as illustrated by the arrow 1520. Accordingly, in someembodiments, the control 1420 may be operably connected to the distalarms 1410 such that actuating the control 1420 applies an axial distalforce, causing the distal arms 1410 to move axially and distally outsidethe distal tube 1510. The distal arms 1410 may be radially biased, suchthat the distal arms 1410 expand radially when moved outside the distaltube 1510. Further, releasing the control 1420 may cause the distal arms1410 to retract proximally, back inside the distal tube 1510 and to anaxial position.

FIG. 16a-b illustrate another embodiment of radially expanding thedistal arms 1210. Referring to FIG. 16a , a PDS 1400 may includelinkages 1610 connected to the distal arms 1410 near the connectionpoints 1450. Actuating the control 1420 can cause the linkages 1610 tomove in the direction shown by the arrow 1620 , thereby radiallyexpanding the distal arms 1410.

In some embodiments, the patch 120, 140 may be parallel to the shaft1430 when it is deployed to the tissue defect 110. The patch 120, 140may be implanted flat on the tissue defect 110 by bending the shaft1430, which can be flexible. In some embodiments, it may be advantageousfor the patch 120, 140 to be parallel to the shaft 1430 due to the angleof insertion or approach to the tissue defect location (e.g. hernia).

FIG. 3 illustrates a compressed patch 120, 140 prepared for loading ontoa PDS 1400. As illustrated in FIG. 3, in some embodiments, the patch120, 140 in a compressed state can resemble the canopy of a closedumbrella. It will be appreciated that the patch 120, 140 may becompressed in a variety of other configurations as well. Referring toFIG. 3, in some embodiments, a compressed patch 120, 140 comprises afolded structure with one or more folding points. Thus, a compressedpatch 120, 140 may define a peak 310, an outer surface 320, and an innersurface 330. In some embodiments, the peak 310 corresponds to thecentral region 850 of a patch 120, 140 when it is expanded to asubstantially planar position. In some embodiments, the patch 120, 140to be loaded onto a PDS 1400 can comprise multiple layers that have beenpre-adhered to each other pre-operatively. For example, two patches 120,140 may be adhered to each other via multiple restricting adhesionpoints to provide rigidity and structural support

FIG. 17 illustrates a compressed patch 120, 140 loaded onto a PDS 1400according to some embodiments of the invention. Referring to FIG. 17,the distal arms 1820 may be positioned over the outer surface 310 of acompressed patch 120, 140. FIG. 18 illustrates a PDS 1400 with distalarms 1410 that are radially expanded. In addition, FIG. 18 illustrates apatch 120, 140 in a substantially planar state attached to the radiallyexpanded distal arms 1410. FIGS. 19a -b, 20 a-b, and 21 a-b, illustratea close up view of the annotated portion of the PDS 1400 illustrated inFIG. 18. Referring to FIGS. 18, 19 a-b, 20 a-b, and 21 a-b, in someembodiments, a PDS 1400 includes grips 1930 toward the distal end of thedistal arms 1410. The grips 1930 may be clips, clamps, pincers,pinchers, grabbers, or the like, that secure the patch 120, 140 to thedistal arms 1410 by holding the patch 120, 140 at the peripheral regionof the patch 120, 140. The PDS 1400 may include a mechanism forcontrolling the release of the grips 1930. The mechanism may furtherallow control of how tightly the grips 1930 hold onto a patch 120, 140.

FIGS. 19a -b, 20 a-b, and 21 a-b illustrates various mechanisms by whichthe grips 1930 can hold and release a patch 120, 140. In someembodiments, a linkage 1910 can be coupled to a grip element 1930through any suitable mechanism, such as mechanical or chemical. FIG. 19aillustrates two grip elements 1930, with a patch 120, 140 in between thegrip elements 1930. As illustrated in FIG. 19b , moving one grip element1930 relative to the other can increase the space between the gripelements 1930, thereby releasing the patch 120, 140. In someembodiments, a linkage 1912 coupled to a grip element 1930 can beutilized to release the patch 120, 140, by moving the linkage 1912 inthe direction of the arrow 1950, as illustrated in FIG. 19a . In someembodiments, actuating the control 1420 on the PDS 1400 can move thelinkage 1910 and thereby release the patch 120, 140.

Referring to FIGS. 20a -b, two grip elements 1930 can be pivotallyconnected at the distal tip of a distal arm 1410. A linkage 1940 can becoupled to a grip element 1930. Referring to FIGS. 20a -b, moving thelinkage 1940 in the direction of the arrow 1950 can increase the anglebetween the two grip elements 1930, thereby releasing the patch 120,140.

Referring to FIG. 21a , a linkage 1940 can extend past the distal arm1410 and then curl underneath the patch 120, 140 and into the patch 120,140 such that the tip of the linkage 1940 forms a coil 2110. The coil2110 can be disposed so that it is inserted through the patch 120, 140or partly through the patch 120, 140, thereby binding the distal arms1410 and the patch 120, 140 together. Referring to FIGS. 21a -b,actuating the control 1420 on the PDS 1400 can cause the linkage 1940 tomove in the direction of the arrow 2150, removing the coil 2110 from thepatch 120, 140 and releasing the patch 120, 140 from the distal arms1410.

FIGS. 22-24 illustrate a PDS 1400 in use to deliver and implant a bottompatch 120 to the inner surface of a tissue defect 110, thereby pluggingthe tissue defect 110. Referring to FIG. 22, a PDS 1400 with a loadedbottom patch 120 is inserted through a tissue defect 110, until theentire length of the distal arms 1410 is distal (below) the tissuedefect 110. Referring to FIGS. 23-24, the control 1420 on the PDS 1400may be actuated, causing the distal arms 1410 to expand radially, andthereby causing the bottom patch 120 to similarly expand, since thedistal arms 1410 are attached to the bottom patch 120 via any of themechanisms described above (e.g., grips 1930 that hold the patch 120).Accordingly, the bottom patch 120 may be expanded on the side distal tothe tissue defect 110. The bottom patch 120 may be expanded from acompressed state to an expanded state that is substantially planar. Thepatch 120 may then be positioned laterally to ensure that the entiretissue defect 110 is plugged by the bottom patch 120. The patch 120 mayalso be moved in a proximal direction, bringing the patch 120 in contactwith the inner surface 130 of the tissue defect 110.

After the expanded bottom patch 120 is brought to the desired position,the distal arms 1410 may be detached from the patch 120. For example,grips 1930 that were holding on to the patch 120 may be released. Inaddition, the control 1420 on the PDS 1200 may be released, causing thedistal arms 1410 to return to an axial position and detach from thepatch 120. In some embodiments, releasing the control 1420 also causesthe distal arms 1410 to retract proximally, thereby detaching from thepatch 120.

After the bottom patch 120 is implanted, a top patch 140 may also beimplanted according to some embodiments of the invention. In someembodiments, only a bottom patch 120 is implanted, and no top patch 120is implanted. In other embodiments, only a top patch 140 is implanted. Atop patch 140 may be implanted to a tissue defect 110 in a similarmanner as the bottom patch 120.

FIGS. 25-27 illustrate a method of implanting a top patch 140 to atissue defect 110. Although FIGS. 25-27 depict a bottom patch 120, itwill be appreciated that the disclosed methods may also be used toimplant a top patch 140 to a tissue defect 110 without a bottom patch120.

Referring to FIG. 25, a PDS 1400 with a loaded compressed top patch 140is positioned over a tissue defect 110. Referring to FIG. 26, a control1420 on the PDS 1400 may be actuated, causing the distal arms 1410 toexpand radially and the top patch 140 to similarly expand. Next, the PDS1400 may be used to move the top patch 140 to a desired position. Forexample, the top patch 140 may be positioned to contact the outersurface of a tissue defect 110 and completely cover the tissue defect110. Referring to FIG. 27, the control 1420 may be released, causing thedistal arms 1410 to return to an axial position and detach from the toppatch 140.

The PDS 1400 may be used with any number of types of patches 120, 140.For example, in some embodiments a compliant patch 120, 140 may be usedwith the PDS 1400. The compliant nature of the patch 120, 140 allows thepatch 120, 140 to be compressed and held by the distal arms 1410. Insome embodiments, the patch 120, 140 may comprise a dural substituteformed by electro-spinning methods, as described in PCT/US2011/040691,the entirety of which is hereby incorporated herein by reference. Thus,in some embodiments, a patch 120, 140 comprising electro-spun fibers maybe used with the PDS 1400. Other examples of patches 120, 140 which maybe used with the PDS 1200 include dural substitutes comprisingresorbable polymer materials, non-resorbable polymeric materials,xenogenic collagen materials, processed collagen materials, processedallogenic tissue, nanofiber dural substitutes, multi-laminar nanofibermaterials, patterned/reinforced nanofiber materials, synthetic (PGLA,PLGA, PCL, PC, PGA, PLA, PPY, PMMA, PEU, PU, etc.), Biologic (collagen,laminim, elastin, fibronectin, fibrin, SIS, dermis, dura, pericardium,fascia lata, etc.), electrospun material, woven materials, and processedhuman tissue (allograft, autograft, xenograft, etc.). In someembodiments, the thickness of the patch 120, 140 is between about 0.1 mmand 4 mm.

In some embodiments, the top patch 140 and/or bottom patch 120 containshape memory, allowing the patch 120, 140 to return from a deformedstate (e.g. compressed state) to its original shape (e.g. planar). Thus,although the distal arms 1410 on a PDS 1400 may help to expand the patch120, 140, the distal arms 1410 may not be necessary for the patch 120,140 to expand when the patch 120, 140 contains shape memory. Further,when the distal arms 1410 are used to expand a patch 120, 140 with shapememory, less force is required to radially expand the distal arms 1410and cause the patch 120, 140 to expand.

FIGS. 28-30 illustrate a method of implanting a multi-laminar repairmatrix that has been pre-adhered pre-operatively 2810, as describedabove with respect to FIG. 10. The pre-adhered multi-laminar repairmatrix 2810 may comprise a top patch 140 and a bottom 120 adhered toeach other at the central regions 850, and un-adhered at the peripheralregions 840, thus defining a slot 860 between the top 140 and bottom 120patches. Referring to FIGS. 28-30, the pre-adhered multi-laminar repairmatrix 2810 may be compressed and loaded onto the distal arms 1410, thenexpanded to a planar state by actuating the control 1420 on the PDS1400. In some embodiments, the pre-adhered multi-laminar matrix 2810 maybe implanted such that the slots 860 receive the tissue surrounding thetissue defect 110 at substantially the same time. In some embodiments,the top and bottom portions of the slot 860 are flexible.

In some embodiments, patches 120, 140 may be pre-loaded onto the distalarms 1210 of the shaft 1430 and further may be pre-customized by type oftissue defect 110. Accordingly, the shape of the patches 120, 140 and/oradhesive 830 may resemble the shape of a tissue defect 110. For example,the patches 120, 140 may have a shape that follows the perimeter of thetissue defect 110. Thus, a physician may select a PDS 1400 with apre-loaded and pre-customized patch 120, 140 according to the type oftissue defect 110 that the physical will repair.

FIG. 31a illustrates a pre-loaded cartridge 3110 according to someembodiments of the invention. FIG. 31b illustrates the contents of thepre-loaded cartridge 3110 according to some embodiments. In someembodiments, the distal arms 1410 are removably attached to the shaft1430 of a PDS 1400. As illustrated in FIG. 31 b, the pre-loadedcartridge 3110 may include a distal shaft 3120 and distal arms 1410 atthe distal end of the distal shaft 3120. The distal shaft 3120 may bedetached from the proximal shaft 1430, as illustrated in FIG. 32.Referring to FIG. 31 b, the pre-loaded cartridge 3110 may also include acompressed patch 120, 140 loaded onto the distal arms 1410, and alinkage 3130 at the proximal end of the distal shaft 3120. In someembodiments, the distal arms 1410 does not include a pre-loadedcompressed patch 120, 140. FIG. 32 illustrates one embodiment of aproximal shaft 1430 removed from the distal shaft 3120. Referring toFIG. 32, in some embodiments the proximal end of the distal shaft 3120may include a linkage 3130. In addition, the distal end of the proximalshaft 1430 may include a linkage 3210. The pre-loaded cartridge 3110 maybe connected to the distal end of the proximal shaft 1430 by connectingthe linkage 3210 in the proximal shaft 1430 to the linkage 3130 in thedistal shaft 312-. The pre-loaded cartridge 3110 and the proximal shaft1430 may also be connected according to any suitable mechanism known inthe art. In some embodiments, the proximal shaft 1430 is re-usable andthe pre-loaded cartridge 3110 and its components are disposable. Thepre-loaded cartridge 3110 may come in a variety of configurations,including those for different types, shapes, and sizes of tissue defects110.

In some embodiments, a kit may be provided and customized for certaintissue defects 110. The kit may advantageously include components suchas a PDS 1400, reloadable cartridges 3110, a multi-laminar repair matrix100, a single laminar repair matrix, saline, sutures, rulers, a gauze,any other surgical dressing, and the like. This kit may be contained ina sterile environment in containers well known in the art. For example,the containers may be plastic bags that are secured and easily opened.All the components inside the kit may be sterilized before beingpackaged in the container.

In some embodiments, the kit may include a reloadable cartridge 3110 anda PDS 1400 detached from the distal shaft 3120 and distal arms 1410. Apatch 120, 140 may be pre-loaded onto the distal arms 1410 packaged inthe reloadable cartridge 3110. In other embodiments, a patch 120, 140may not be pre-loaded and may be separate from the distal arms 1410packaged in the reloadable cartridge 3110. The patch 120, 140 may besized and shaped to repair a certain tissue defect 110 of a similar sizeand shape. In addition, the kit may include a selection of severalpatches 120, 140 likely to work in the environment of a surgicalprocedure leaving a tissue defect 110 of a particular size and shape.For example, the kit may include a selection of several patches 120, 140all having a triangular shape but having a different size in order toaccommodate tissue defects 110 of varying sizes. The triangular shapedpatches 120, 140 may be optimized for surgical repair of defects 110 inthe posterior fossa, such as surgical repair of Chiari malformations. Inaddition, the triangular shaped patches may have a base with a length ofabout 0.5 cm and 10 cm, a height between about 1 cm and 20 cm, andangles at the vertices of the triangular shaped patch 120, 140 betweenabout 5° to about 85°. As another example, the kit may include aselection of several patches 120, 140 having different shapes in orderto accommodate tissue defects 110 of varying shapes. In someembodiments, the kit may include a PDS 1400 attached to the distal arms1410. In other embodiments, the kit may include a reloadable cartridge3110 and no PDS 1400. Any combination of components may be included inthe kit. In some embodiments, the components are customized for certaintissue defects. For example, as explained above, the shape, size, andconfiguration of the patches 120, 140 and/or adhesives 830 may becustomized.

In some embodiments, the PDS 1400 may be disposable after a single use.In other embodiments, the PDS 1400 may be re-usable. In someembodiments, the PDS 1400 is adapted to receive loadable cartridgescontaining patches.

Various modifications to the implementations described in thisdisclosure may be readily apparent to those skilled in the art, and thegeneric principles defined herein may be applied to otherimplementations without departing from the spirit or scope of thisdisclosure. Thus, the claims are not intended to be limited to theimplementations shown herein, but are to be accorded the widest scopeconsistent with this disclosure, the principles and the novel featuresdisclosed herein. Certain features that are described in thisspecification in the context of separate embodiments also can beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment alsocan be implemented in multiple embodiments separately or in any suitablesubcombination. Moreover, although features may be described above asacting in certain combinations and even initially claimed as such, oneor more features from a claimed combination can in some cases be excisedfrom the combination, and the claimed combination may be directed to asubcombination or variation of a subcombination.

Similarly, while operations may be described as occurring in aparticular order, this should not be understood as requiring that suchoperations be performed in the particular order described or insequential order, or that all described operations be performed, toachieve desirable results. Further, other operations that are notdisclosed can be incorporated in the processes that are describedherein. For example, one or more additional operations can be performedbefore, after, simultaneously, or between any of the disclosedoperations. In certain circumstances, multitasking and parallelprocessing may be advantageous. Additionally, other embodiments arewithin the scope of the following claims. In some cases, the actionsrecited in the claims can be performed in a different order and stillachieve desirable results.

1.-29. (canceled)
 30. A repair matrix for repairing a tissue defect, therepair matrix comprising: a top flexible patch, the top flexible patchcomprising material that facilitates tissue growth; a bottom flexiblepatch, the bottom flexible patch comprising material that facilitatestissue growth, wherein a periphery of the bottom flexible patchcomprises an adhesive; and a connecting portion connecting anon-peripheral portion of the top flexible patch with a non-peripheralportion of the bottom flexible patch, the connecting portion comprisinga height adapted to prevent adhesion of the bottom flexible patch to thetop flexible patch, wherein the top flexible patch comprises a firstbiodegrade time, the bottom flexible patch comprises a second biodegradetime, and the adhesive comprises a third biodegrade time, wherein thethird biodegrade time is longer than the first biodegrade time and thesecond biodegrade time.
 31. The repair matrix of claim 1, wherein one orboth of the top flexible patch and the bottom flexible patch compriseselectro-spun fibers.
 32. The repair matrix of claim 1, wherein one orboth of the top flexible patch and the bottom flexible patch compriseswholly synthetic dural substitute material.
 33. The repair matrix ofclaim 1, wherein one or both of the top flexible patch and the bottomflexible patch is configured to biodegrade after being implanted totissue surrounding a tissue defect.
 34. The repair matrix of claim 33,wherein the tissue defect is a dural defect.
 35. The repair matrix ofclaim 1, wherein a peripheral portion of the top flexible patchcomprises an adhesive.
 36. The repair matrix of claim 1, wherein a shapeof the top flexible patch substantially matches a shape of the bottomflexible patch.
 37. The repair matrix of claim 1, wherein a shape of thetop flexible patch is different from a shape of the bottom flexiblepatch.
 38. The repair matrix of claim 1, wherein one or both of the topflexible patch and the bottom flexible patch comprises shape memorymaterial.
 39. The repair matrix of claim 1, wherein the height of theconnecting portion is adjustable to substantially match a width oftissue surrounding a tissue defect.
 40. The repair matrix of claim 1,wherein the connecting portion connecting the non-peripheral portion ofthe top flexible patch with the non-peripheral portion of the bottomflexible patch comprises an adhesive.
 41. The repair matrix of claim 1,wherein the connecting portion connecting the non-peripheral portion ofthe top flexible patch with the non-peripheral portion of the bottomflexible patch comprises a same material as the material of the topflexible patch and/or the bottom flexible patch.
 42. A kit for repairinga dural defect, comprising: a sterile packet containing a plurality ofbiodegradable patches, wherein the plurality of biodegradable patchescomprise varying sizes, wherein each of the plurality of biodegradablepatches comprises material that facilitates tissue growth, wherein aperiphery of one or more of the plurality of biodegradable patchescomprises an adhesive for adhering the biodegradable patch to a surfaceof tissue surrounding a tissue defect, and wherein the one or more ofthe plurality of biodegradable patches comprises a first biodegradetime, and the adhesive of the one or more of the plurality ofbiodegradable patches comprises a second biodegrade time, wherein thesecond biodegrade time is longer than the first biodegrade time.
 43. Thekit of claim 42, wherein each of the plurality of biodegradable patchescomprises a shape that is square, rectangular, circular, triangular,elliptical, hexagonal, or quadrilateral.
 44. The kit of claim 42,wherein each of the plurality of biodegradable patches comprises shapememory material.
 45. The kit of claim 42, wherein each of the pluralityof biodegradable patches comprises electro-spun fibers.
 46. The kit ofclaim 42, wherein each of the plurality of biodegradable patchescomprises wholly synthetic dural substitute material.
 47. A repairmatrix for repairing a tissue defect, comprising: a flexible patch, theflexible patch comprising a material formed by electrospinning thatfacilitates tissue growth, wherein the flexible patch in a first stateis configured to be compressed to facilitate implantation of theflexible patch to tissue surrounding a tissue defect, and the flexiblepatch in a second state is configured to be expanded such that theflexible patch substantially conforms to a curvature of the tissuesurrounding the tissue defect, wherein a periphery of the flexible patchin the second state comprises an adhesive for adhering the flexiblepatch to the tissue surrounding the tissue defect, wherein the flexiblepatch comprises a first biodegrade time, and the adhesive comprises asecond biodegrade time, wherein the second biodegrade time is longerthan the first biodegrade time.
 48. The repair matrix of claim 47,wherein the flexible patch is configured to biodegrade after beingimplanted to the tissue surrounding a tissue defect.
 49. The repairmatrix of claim 47, wherein the flexible patch comprises whollysynthetic dural substitute material.